title: MRI and cerebrospinal fluid biomarkers for predicting progression to Alzheimer's disease in patients with mild cognitive impairment: a diagnostic accuracy study.
abstract: OBJECTIVE
  To assess the incremental value of MRI and cerebrospinal fluid (CSF) analysis after a short memory test for predicting progression to Alzheimer's disease from a pragmatic clinical perspective.
  
  
  METHODS
  Diagnostic accuracy study in a multicentre prospective cohort study.
  
  
  METHODS
  Alzheimer Disease Neuroimaging Initiative participants with complete data on neuropsychological assessment, MRI of the brain and CSF analysis.
  
  
  METHODS
  Patients with mild cognitive impairment (MCI; n=181) were included. Mean follow-up was 38.9 months (range 5.5-75.9).
  
  
  METHODS
  Diagnostic accuracy of individual instruments and incremental value of entorhinal cortex volume on MRI and p-τ/Aβ ration in CSF after administration of Rey's Auditory Verbal Learning Memory Test are calculated and expressed as the 'Net Reclassification Improvement' (NRI), which is the change in the percentage of individuals that are correctly diagnosed as Alzheimer or non-Alzheimer case.
  
  
  RESULTS
  Tested in isolation, a short memory test, MRI and CSF all substantially contribute to the differentiation of those MCI patients who remain stable during follow-up from those who progress to develop Alzheimer's disease. The memory test, MRI and CSF improved the diagnostic classification by 21% (95% CI 15.1 to 26.9), 22.1% (95% CI 16.1 to 28.1) and 18.8% (95% CI 13.1 to 24.5), respectively. After administration of a short memory test, however, the NRI of MRI is +1.1% (95% CI 0.1 to 3.9) and of CSF is -2.2% (95% CI -5.6 to -0.6).
  
  
  CONCLUSIONS
  After administration of a brief test of memory, MRI or CSF do not substantially affect diagnostic accuracy for predicting progression to Alzheimer's disease in patients with MCI. The NRI is an intuitive and easy to interpret measure for evaluation of potential added value of new diagnostic instruments in daily clinical practice.
authors.affiliation: Department of Neurology, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: Edo
authors.initials: E
authors.lastname: Richard
authors.forename: Ben A
authors.initials: BA
authors.lastname: Schmand
authors.forename: Piet
authors.initials: P
authors.lastname: Eikelenboom
authors.forename: Willem A
authors.initials: WA
authors.lastname: Van Gool
keywords: Alzheimer; Mild cognitive impairment; Net reclassification improvement; diagnostic accuracy